Diseases

  • Article
    | Open Access

    Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco.

    • Isobel Routledge
    • , Adrienne Epstein
    •  & Isabel Rodriguez-Barraquer
  • Article
    | Open Access

    New-onset hyperglycemia and complications of preexisting diabetes have been observed in COVID-19 patients, however, the underlying mechanisms are not fully understood. Here, the authors show that SARS-CoV-2 is detectable in both endocrine and exocrine cells of the pancreata of patients with COVID-19.

    • Charlotte Steenblock
    • , Stefanie Richter
    •  & Stefan R. Bornstein
  • Article
    | Open Access

    Restricted and repetitive behaviors (RRBs) are a core clinical feature of autism, yet the brain basis of RRBs is unknown. Here, the authors demonstrate that aberrant cognitive control and motor circuit dynamics differentially predict three distinct symptom clusters that define RRBs.

    • Kaustubh Supekar
    • , Srikanth Ryali
    •  & Vinod Menon
  • Article
    | Open Access

    Technical advancements have significantly improved early diagnosis of cervical cancer, but accurate diagnosis is still difficult due to various practical factors. Here, the authors develop an artificial intelligence assistive diagnostic solution to improve cervical liquid-based thin-layer cell smear diagnosis according to clinical TBS criteria in a large multicenter study.

    • Xiaohui Zhu
    • , Xiaoming Li
    •  & Yanqing Ding
  • Article
    | Open Access

    Some patients with COVID-19 fail to clear the viral infection quickly, yet our understanding for the underlying immune characteristics is still lacking. Here the authors use single-cell RNA sequencing and other data form such patients to show that persistent infection is associated with immune suppression and reduced expression of ribosomal protein genes.

    • Bin Yang
    • , Junpeng Fan
    •  & Chaoyang Sun
  • Article
    | Open Access

    Penetrance of variants in monogenic disease and clinical utility of common polygenic variation has not been well explored on a large-scale. Here, the authors use exome sequencing data from 77,184 individuals to generate penetrance estimates and assess the utility of polygenic variation in risk prediction of monogenic variants.

    • Julia K. Goodrich
    • , Moriel Singer-Berk
    •  & Miriam S. Udler
  • Article
    | Open Access

    Many job sectors classified as ‘essential’ have continued operating with limited restrictions during the COVID-19 pandemic, potentially placing workers at higher risk of infection. Here, the authors show that seropositivity rates in workers vary widely across and between job sectors in Geneva, Switzerland.

    • Silvia Stringhini
    • , María-Eugenia Zaballa
    •  & Idris Guessous
  • Article
    | Open Access

    Matthew M. Hernandez and Ana S. Gonzalez-Reiche and colleagues report evidence of SARSCoV-2 infections in respiratory pathogen-negative nasopharyngeal specimens collected in New York, which date back to over one month before the first officially documented case in the state. The findings provide insights in to the origins of the virus in New York.

    • Matthew M. Hernandez
    • , Ana S. Gonzalez-Reiche
    •  & Emilia Mia Sordillo
  • Article
    | Open Access

    Genetic variants in CD36 have been associated with metabolic syndrome. Here, the authors found that lymphatic vessel integrity and lipid transport are influenced by CD36 expression, and lymphatic endothelial cell CD36 deficiency causes visceral obesity and insulin resistance, which are risk factors for metabolic syndrome and diabetes.

    • Vincenza Cifarelli
    • , Sila Appak-Baskoy
    •  & Nada A. Abumrad
  • Article
    | Open Access

    Impaired wound healing is a serious complication in diabetic patients, and is associated with reduced HIF1α stability. Here, the authors design a small molecule that stabilizes HIF1α by blocking its interaction with VHL and show that it promotes wound healing in mouse models of diabetes.

    • Guodong Li
    • , Chung-Nga Ko
    •  & Chung-Hang Leung
  • Article
    | Open Access

    During insulin-resistance, the compensatory expansion of beta-cell mass is able to delay or the onset of overt type 2 diabetes. Here, the authors report that beta-arrestin-1, an intracellular protein known to regulate signalling through G protein-coupled receptors, is essential for beta-cell replication and function in insulin-resistant mice.

    • Luiz F. Barella
    • , Mario Rossi
    •  & Jürgen Wess
  • Article
    | Open Access

    Mechanisms underlying the cardiotoxicity associated with thoracic irradiation and doxorubicin treatment during anticancer therapy remain poorly understood. Here the authors show that treatment with an antibody against the L1 cell adhesion molecule inhibits nuclear L1CAM translocation, thereby controlling vascular DNA damage and preventing cardiotoxicity.

    • Jae-Kyung Nam
    • , A-Ram Kim
    •  & Yoon-Jin Lee
  • Article
    | Open Access

    Here, using diagnostic tools in a longitudinal cohort of ZIKV-infected pregnant women of the French Guiana Western Hospital Center (CHOG) and their infants, the authors investigate the long term neuropathological effects of congenital infection, finding that a laboratory confirmed congenital ZIKV infection at birth is associated with higher risks of adverse neurological outcomes up to three years of life.

    • Najeh Hcini
    • , Yaovi Kugbe
    •  & Léo Pomar
  • Article
    | Open Access

    As the leading cause of vision loss in working-age adults, diabetic retinopathy requires routinely retinal screening. Here the authors develop a deep learning system that can facilitate the screening by providing real-time image quality assessment, lesions detection, and grades across the disease spectrum.

    • Ling Dai
    • , Liang Wu
    •  & Weiping Jia
  • Article
    | Open Access

    Open fires can increase heavy exposure to hazardous particulate matters, and thus harm human health, particularly among the vulnerable individuals, such as pregnant women. Here, the authors show an association between maternal exposure to fire smoke and increased risk of pregnancy loss in South Asia.

    • Tao Xue
    • , Guannan Geng
    •  & Tong Zhu
  • Article
    | Open Access

    There are currently no drugs available to treat SARS-CoV-2 infection. A promising alternative treatment for COVID-19 patients is convalescent plasma. Here, Gharbharan et al. collect covalescent plasma and report no overall clinical benefit for 86 patients hospitalized for COVID-19 and treated with 300 mL convalescent plasma.

    • Arvind Gharbharan
    • , Carlijn C. E. Jordans
    •  & Bart J. A. Rijnders
  • Article
    | Open Access

    Here the authors use single-cell RNA-seq to profile the transmission stages of the human malaria parasite Plasmodium falciparum as it progresses through the Anopheles mosquito. They highlight unique patterns of gene usage throughout this development and identify potential pleiotropic genes that function at multiple life cycle stages.

    • Eliana Real
    • , Virginia M. Howick
    •  & Mara K. N. Lawniczak
  • Article
    | Open Access

    Bacterial or viral infection can lead to lethal systemic inflammation and thrombosis. Here, the authors show that inhibiting integrin outside-in signaling in leukocytes and platelets alleviates inflammation/clotting and improved survival in septic mice.

    • Ni Cheng
    • , Yaping Zhang
    •  & Xiaoping Du
  • Article
    | Open Access

    Heterozygous HNF1A mutations can give rise to maturity onset diabetes of the young 3 (MODY3), characterized by insulin secretion defects. Here the authors show that MODY3-related HNF1A mutation in patient hiPSCderived pancreatic cells decreases glucose transporter GLUT2 expression due to compromised DNA binding.

    • Blaise Su Jun Low
    • , Chang Siang Lim
    •  & Adrian Kee Keong Teo
  • Article
    | Open Access

    The percentage of national populations infected during the first stages of the COVID-19 pandemic are unclear owing to limited early testing. Here the authors provide a nation-wide prevalence study of SARS-CoV-2 antibodies in France from the first wave of COVID-19 in 2020, including stratification based on age, sex and region.

    • Stéphane Le Vu
    • , Gabrielle Jones
    •  & Harold Noel
  • Article
    | Open Access

    Lung resident memory T (TRM) cells are important for protection from viral infection in the lungs. Here the authors use paired lung biopsy material and blood to characterize T cell responses in patients with COVID-19 over time and find persistence of antiviral lung TRM cells that might be important to limit reinfection.

    • Judith Grau-Expósito
    • , Nerea Sánchez-Gaona
    •  & Meritxell Genescà
  • Article
    | Open Access

    Influenza forecasting in the United States is challenging and consequential, with the ability to improve the public health response. Here the authors show the performance of the multiscale flu forecasting model, Dante, that won the CDC’s 2018/19 national, regional and state flu forecasting challenges.

    • Dave Osthus
    •  & Kelly R. Moran
  • Article
    | Open Access

    Idiopathic pulmonary fibrosis (IPF) is a fatal adult lung disease. Here the authors investigate the functional significance of PDCD5 in club cells as a mediator of lung fibrosis and potential therapeutic target for IPF.

    • Soo-Yeon Park
    • , Jung Yeon Hong
    •  & Ho-Geun Yoon
  • Article
    | Open Access

    In placental malaria, interactions between parasite protein VAR2CSA and human glycosaminoglycan chondroitin sulfate A (CS) sequesters infected red blood cells in the placenta. Here, the authors provide cryo-EM structures of VAR2CSA and placental CS, identifying molecular interactions that could guide design of placental malaria vaccines.

    • Kaituo Wang
    • , Robert Dagil
    •  & Ali Salanti
  • Article
    | Open Access

    Generics contribute to increased availability of antibiotics, benefiting healthcare systems but potentially leading to increased consumption with implications for antibiotic stewardship and resistance. Here, the authors found no consistent changes in prescribing patterns of the 13 antibiotics that entered the US market as generics from 2000–2012.

    • Cecilia Kållberg
    • , Jemma Hudson
    •  & Ramanan Laxminarayan
  • Article
    | Open Access

    Differences in thalamic structure have been observed in several psychiatric disorders, but the genetic overlap has not been explored. Here, the authors perform a genome-wide association study on thalamic nuclei volume and find genetic loci in common between thalamic volumes and brain disorders.

    • Torbjørn Elvsåshagen
    • , Alexey Shadrin
    •  & Tobias Kaufmann
  • Article
    | Open Access

    Proteolysis targeting chimeras (PROTACs) is an effective alternative to modulate protein homeostasis but can lead to uncontrollable protein degradation and off-target side effects. Here, the authors developed semiconducting polymer nano-PROTACs with phototherapeutic and activatable protein degradation abilities for photo-immunometabolic cancer therapy.

    • Chi Zhang
    • , Ziling Zeng
    •  & Kanyi Pu
  • Article
    | Open Access

    Although enterovirus D68 poses a major global threat to children, neither vaccines nor therapeutics are currently available. Using Cryo-EM, Zhang et al. show that two murine-derived monoclonal antibodies with therapeutic efficacy neutralize virions via binding to the canyon region, creating steric hindrance for sialic acid receptor binding.

    • Chao Zhang
    • , Cong Xu
    •  & Zhong Huang
  • Article
    | Open Access

    CRISPR-Cas9 is a gene editing tool that can be used to modulate gene expression. Here, the authors report the generation of a mouse model that express all components of the CRISPR-Cas9 guide directed Synergistic Activation Mediator (SAM), demonstrate that gene activation can be achieved with various delivery methods and include generation of a disease model of hypercholesterolemia

    • Charleen Hunt
    • , Suzanne A. Hartford
    •  & Guochun Gong
  • Article
    | Open Access

    Estimates of COVID-19-related mortality are limited by incomplete testing. Here, the authors perform counterfactual analyses and estimate that there were 59,000–62,000 deaths from COVID-19 in Italy until 9th September 2020, approximately 1.5 times higher than official statistics.

    • Chirag Modi
    • , Vanessa Böhm
    •  & Uroš Seljak
  • Article
    | Open Access

    Several prognostic indices are available to predict the long-term fate of emerging infectious diseases and the effect of their containment measures, including a variety of reproduction numbers. Here, the authors introduce the epidemicity index, a complementary index to evaluate the potential for transient increases of SARS-Cov-2 epidemics.

    • Lorenzo Mari
    • , Renato Casagrandi
    •  & Marino Gatto
  • Article
    | Open Access

    Aortic aneurysm and dissection, the major problem linked to Marfan syndrome (MFS), lacks effective pharmacological treatment. Here, the authors show that the NO pathway is overactivated in MFS and that inhibition of guanylate cyclase and cGMP-dependent protein kinase reverts MFS aortopathy in mice.

    • Andrea de la Fuente-Alonso
    • , Marta Toral
    •  & Juan Miguel Redondo
  • Article
    | Open Access

    Placental dysfunction can have catastrophic or barely discernible effects ranging from miscarriage to apparently normal birth. Here the authors present a comprehensive analysis of the human placental transcriptome and identify circular RNAs and piRNAs.

    • Sungsam Gong
    • , Francesca Gaccioli
    •  & D. Stephen Charnock-Jones
  • Article
    | Open Access

    Leptin can rescue hyperglycemia in type 1 diabetes, but the underlying mechanisms for this effect are not clear. Here, the authors report that leptin action is mediated by inhibition of the heightened activity of arcuate GABA neurons in murine models of type 1 diabetes through restoring nutrient sensing.

    • Shengjie Fan
    • , Yuanzhong Xu
    •  & Qingchun Tong